Humoral and cellular immune responses in critically ill influenza A/H1N1-infected patients.

There is limited knowledge of influenza-specific immune responses and their kinetics in critically ill patients. We investigated humoral and cellular immune responses after critical influenza A/H1N1 infection and hypothesized that dysfunctionality or absence of immune responses could contribute to more severe illness. We followed 12 patients hospitalized with severe influenza infection; the majority admitted to intensive care unit (ICU). Blood samples were collected at days 10 and 19 and at 5 months. Antibody responses to surface glycoproteins haemagglutinin (HA) and neuraminidase (NA) of A/H1N1pdm09 were quantified by haemagglutination inhibition (HAI), microneutralization (MN), Enzyme-linked immunosorbent assay (ELISA) and Enzyme-linked lectin assay (ELLA). Influenza-specific antibody levels and avidity were measured separately for head and stalk domains of H1. Cytokine secreting CD4+ and CD8+ T cell responses to conserved influenza epitopes (M1, NP and PB1) were analysed by FluoroSpot. Overall, the patients retained a high level of functional HA- and NA-specific antibodies over the study period. During the acute phase (up to 3 weeks from symptom onset), antibodies specific to H1 stalk increased earlier and were present in higher amount compared with H1 head-specific antibodies. The NA-specific antibodies and the non-neutralizing HA-specific antibody response for H1 head and H1 full-length showed a significant decline from acute to convalescent phase. Despite high total IgG concentrations, avidity to H1 head and H1 full-length protein remained low at all time points. Similarly, CD8+ T cell responses were continuously measured at low levels. In conclusion, our study found that critically ill patients were characterized by low HA-specific antibody avidity and CD8+ T cell response.

Fetal Exposure to Preeclampsia and Later Risk of Cardiometabolic Disorders: A Population-Based Cohort Study.

BACKGROUND: Fetal preeclampsia exposure has been associated with later cardiometabolic disease. However, this association has been investigated in few large population-wide studies, and it is unknown whether the association represents a causal relationship or is the result of shared etiological factors. METHODS: To further investigate the relationship between preeclampsia exposure and later cardiometabolic disease, we identified 1 692 944 singleton infants born in Norway during 1967 to 1997, where 44 299 were exposed to preeclampsia in utero. The individuals were followed for hypertension, diabetes, and dyslipidemia as defined by dispensed medication. We used Cox regression models to calculate the association between preeclampsia exposure and cardiometabolic outcomes adjusting for measured confounders. We also used full sibling comparisons and stratified Cox regression to control for unmeasured familial confounders. RESULTS: On the population level, exposed individuals had increased risk of hypertension (adjusted hazard ratio [aHR] 1.51 [95% CI, 1.41-1.63]), diabetes (aHR 1.33 [95% CI, 1.24-1.43], and dyslipidemia (aHR 1.28 [95% CI, 1.13-1.45]) compared with unexposed individuals. In sibling data, individuals not exposed to preeclampsia, but with an exposed sibling, had higher risk of hypertension and diabetes than individuals where no siblings were exposed to preeclampsia. Moreover, when comparing siblings discordant on preeclampsia exposure, there were no associations between preeclampsia and hypertension (aHR 1.05 [95% CI, 0.88-1.26]), diabetes (aHR 0.96 [95% CI, 0.80-1.14]), and dyslipidemia (aHR 0.86 [95% CI, 0.62-1.20]). CONCLUSIONS: Fetal preeclampsia exposure was associated with adult life hypertension, diabetes, and dyslipidemia, but these associations were likely due to shared etiological factors, rather than exposure to the preeclamptic condition itself.